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What is the biggest risk factor for getting CV disease?
hypertension
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What does hypertension do specifically to increase the risk of CV disease?
- increased hypertrophy of left ventricle
- increased risk of CAD
- increased norepinephrine
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What is the goal BP for a normal person?
120/80
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What is the goal BP for a diabetic?
140/90
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What is the second biggest risk factor for developing CV disease?
- Diabetes
- **Altered protein function
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How can you directly target or lower the risk of CHD in a diabetic patient?
lower the hemoglobin A1C
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What are AGEs?
advanced glycation endproducts
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What is the third greatest risk factor for developing CV disease?
hyperlipidemia/obesity
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What are some common biomarkers associated with hyperlipidemia?
- BMI greater than 25 kg/m2HDL lower than 50 mg/dL
- TG greater than 150 mg/dL
- LDL greater than 70 mg/dL
- Total Cholesterol
- Lipid ratios
- Ratio of apo B/A-1 (apolipoproteins)
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What do C-Reactive Proteins have to do with CV disease?
- they are a sign of inflammation and a risk factor for CV disease
- made in the liver
- clearly associated with increased risk in men (not nec. women)
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What is the only recommended marker of inflammation at this point in time?
hsC-Reactive Protein (hsCRP)
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What is hsCRP?
- an acute phase inflammatory protein produced in the hepatocytes of the liver
- increased during any systemic infection
- its exact role in the body is unknown, but it might contribute to innate immunity and suppression of autoimmunity
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What types of infections might you see elevated levels of hsCRP?
- gingivitis
- prostatitis
- bronchitis
- UTI
- Cancer
- gastric inflammation
- arthritis
- hormone replacement therapy
- smoking
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What other markers (besides CRP assay) could show presence of inflammation, but are more difficult to perform?
- oxidized low-density lipoproteins
- cytokines
- adhesion molecules
- fibrinogen
- SAA (serum amyloid A)
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What used to be a popular way to lower homocysteine levels?
consuming large amounts of folic acid and B vitamins
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Are increased homocysteine levels bad for you (increase CV risk)?
used to think so, but not so much anymore
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Do B vitamins and folic acid really have a benefit in reducing CV disease?
no, they may lower the levels, but there is no hard evidence
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What do elevated levels of homocysteine put you at risk for?
- forming a clot
- high levels modify fibrinogen lysine by thiolactone
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What are the three main potential issues with homocysteine?
- modification of fibrinogen
- modification of fibronectin
- modification of cytochrome C
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This molecule probably plays a role in artherosclerotic plaque formation but is NOT a cause of CVD?
homocysteine
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Name some lifestyle habits that would increase your risk for CVD.
- poor diet
- alcohol abuse
- smoking
- lack of physical exercise
- sleep disorder breathing (apnea)
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Which increased serum level would indicate an increased risk for CVD?
GGT (gamma-glutamyltransferase): a liver enzyme
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T/F: Genetic factors can increase your risk for CVD.
true
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Can you reverse left ventricle hypertrophy and hypertension? If so, how?
Yes, with beta 1 selective beta blockers (must be started early)
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What neurotransmitter causes left ventricular hypertrophy in excessive amounts?
norepinephrine
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Which cardiac drug class is absolutely critical to be used in acute heart failure?
diuretics
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What part of the inflammatory immune process does CRP affect when it binds to phosphocholine groups in cell membranes?
complement activation
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What is the primary mechanism of diuretics?
direct inhibition of sodium transport at one or more of the four major anatomical sites in the nephron where sodium reabsorption occurs
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What are 3 telltale signs that someone might have acute heart failure, but are usually overlooked?
- use more pillows
- shoes don't fit
- dry cough attributed to something else
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What are five under-appreciated aspects of acute heart failure?
- 50% have systemic HTN (greater than 140)
- 40% have preserved left ventricular ejection fraction
- kidney problems
- elderly
- process of care is important
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What does 'wet' mean (in respect to heart failure)?
patient comes into ER with a large amount of fluid retention
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_____ are classified by their electrolyte excretion patterns?
Diuretics
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What makes each type of diuretic agent have a unique action on different locations of the nephron in the kidney?
rigid structural features
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What is SAR and what is it's significance?
- Structure Activity Relationship
- it is data for diuretics that was determined in humans and animals, but can give misleading efficacy data
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What are the 6 different types of diuretics classified according to electrolyte excretion patterns?
- Natriuretic
- Chloruretic
- Saluretic
- Kaliuretic
- Bicarbonaturetic
- Calciuretic
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Which of the 6 types of diuretics is the most effective?
Natriuretic
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This diuretic enhances sodium excretion?
Natriuretic
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This diuretic enhances chloride excretion?
Chloruretic
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This diuretic enhances both sodium and chloride excretion?
Saluretic
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This diuretic enhances potassium excretion?
Kaliuretic
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This diuretic enhances sodium bicarbonate excretion?
Bicarbonaturetic
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This diuretic enhances calcium excretion?
Calciuretic
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Each renal tubule contains 4 functional areas that diurectics act on. Name the 4.
- Proximal tubule
- Loop of Henle
- Distal convoluted tubule
- Collecting tubule
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Where do the most potent diuretics act in the renal tubules?
Loop of Henle
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What is the main function of the proximal tubules in the kidney?
resorption of Sodium, Potassium, Chloride, and all glucose and amino acids by active transport
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The interstitial fluid in this area of the kidney has an increasing osmotic pressure gradient (280 to 1400 mOsm/L)?
Loop of Henle
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10% of filtered water is reabsorbed here?
descending limb of Loop of Henle
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25% of filtered sodium and chloride are reabsorbed here?
ascending limb of Loop of Henle
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What does carbonic anhydrase do in the kidney?
- creates an electrochemical gradient that aids in sodium reabsorption by proton exchange
- carbon dioxide + water = H+ and HCO3-
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Each kidney contains approximately how many nephrons?
1 million
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What is the juxtaglomerular apparatus?
it is the connection between the ascending limb of the Loop of Henle and the glomerulus
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What is the function of the juxtaglomerular apparatus?
- feedback regulation of blood flow and GFR
- secretion of renin
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66% of water is reabsorbed where in the kidney?
Proximal tubules
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What are three important factors to consider about diuretics?
- Potency
- Efficacy
- Relative potency
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Define potency.
the amount of drug (mg/kg) needed to produce a desired effect
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Define relative potency.
- a means of comparing two diuretics as expressed as a ratio of "equi-effective doses"
- a small dose of Drug A compared to a large dose of Drug B
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